Abstract
ObjectiveTo detect the expression of high‐mobility group box protein 1 (HMGB1) and toll‐like receptor 4 (TLR4) and their downstream signaling factors—myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF‐κB), and tumor necrosis factor alpha (TNF‐α)—in the sera of patients with Parkinson's disease (PD) in order to evaluate the relationship of the HMGB1–TLR4 axis with PD development and progression.MethodsThe serum HMGB1 and TLR4 protein levels of 120 patients with PD and 100 healthy volunteers were measured using double‐antibody sandwich ELISA, and their correlations with PD staging, disease duration, drug treatment effectiveness, and clinical classification were analyzed. In addition, their correlations with the key downstream factors of the HMGB1–TLR4 axis (MyD88, NF‐κB, and TNF‐α) were analyzed.ResultsHMGB1 and TLR4 expressions were higher in the peripheral blood of patients with PD than in healthy volunteers. PD patients with poor drug treatment outcomes had significantly higher HMGB1 and TLR4 expressions than PD patients with stable drug treatment outcomes. Higher HMGB1 and TLR4 expressions were found in patients at higher PD stages, and patients with >4‐year disease duration had significantly higher HMGB1 and TLR4 expressions than patients with <4‐year disease duration. No significant difference in HMGB1 and TLR4 expressions was found among patients with tremor‐dominant, akinetic‐rigid, and mixed subtypes of PD. NF‐κB and TNF‐α expressions were positively correlated with high expression of the HMGB1–TLR4 axis.ConclusionHigh expression of the HMGB1–TLR4 axis is closely associated with PD development, progression, drug treatment effectiveness, staging, and disease duration and has great significance for PD diagnosis and treatment.
Highlights
Parkinson’s disease (PD) is a common neurological disorder in the elderly, with the basic pathological feature of the loss of substantia nigra and striatum dopaminergic neurons and the clinical manifestations of resting tremor, bradykinesia, muscle rigidity, and abnormal posture and pace (Zesiewicz, Sullivan, & Hauser, 2017)
This study examined the expression of the high-mobility group box 1 (HMGB1)–toll- like receptor 4 (TLR4) axis and its downstream myeloid differentiation factor 88 (MyD88), NF-κB, and TNF-α factors in 120 patients with PD and 100 healthy volunteers to evaluate its relationship with PD staging, PD duration, and PD drug therapeutic outcomes
We found that the HMGB1–TLR axis downstream signaling factors, MyD88, NF-κB, and TNF-α, were highly expressed in the sera of patients with PD, indicating a connection between the upstream and downstream signaling of the HMGB1–TLR4 axis that plays an important role in the neuritis of PD
Summary
Parkinson’s disease (PD) is a common neurological disorder in the elderly, with the basic pathological feature of the loss of substantia nigra and striatum dopaminergic neurons and the clinical manifestations of resting tremor, bradykinesia, muscle rigidity, and abnormal posture and pace (Zesiewicz, Sullivan, & Hauser, 2017). The main receptors of HMGB1 on the surface of macrophages have been found to be TLR2 and TLR4, and TLR4 played an important role in neural disease (Ohtsu et al, 2017). A previous study showed that HMGB1 induced the expression of interleukin (IL)-6 and other inflammatory cytokines in brain tissues (Kiiski et al, 2017). Expression of this neuroinflammatory cytokine promotes neuron apoptosis and increases the development and progression of neurodegenerative disease in the central nervous system. In the study of AD, the expression of HMGB1 was coexisting with the senile plaques induced by β-amyloid peptide (Aβ) It can promote the binding of Aβ and inhibit the phagocytosis and removal of microglia (Frank et al, 2015). This study evaluated the relationship between the expression of HMGB1 and its receptor, toll- like receptor 4 (TLR4), and the development and progression of PD
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